tbuckley/cabot-search huggingface dataset:
Assessing the marginal costs of radiation therapy and antiestrogen therapy for post-lumpectomy, early-stage breast cancer across Medicaid and Medicare plans.
Authors: Victoria Wu, Martha Khlopin, Reshma Jagsi, Shearwood McClelland
Journal: Journal of Clinical Oncology (2023)

529 Background: With recent Level I evidence (FAST FORWARD) supporting radiation therapy (RT) duration as short as one week and Level I evidence (CALGB9343) supporting RT omission in favor of antiestrogen endocrine therapy (ET) alone in select patients, the necessity of both RT and ET, adjuvantly, in early-stage breast cancer (BC) has been questioned. Evidence providing granular details on the role of insurance in the aggregate cost of RT and ET is lacking. This project disaggregates costs by insurance plan to increase transparency of out-of-pocket (OOP) cost estimates. Methods: National Comprehensive Cancer Network guidelines were utilized to determine the proper treatments, with FAST FORWARD radiation dose/fractionation (26 Gy in 5 fractions) representing RT. Treatments were identified using Current Procedural Terminology and Healthcare Common Procedure Coding System codes. OOP costs, deductibles, and copay/coinsurance were calculated for Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D Rx. The medicare.gov, medicaid.oh.gov, aarpmedicareplans.com, and cms.gov were used to determine pricing. Price estimates reflect actual costs per insurance plan rather than costs estimated from claims data. All procedures were considered to be performed in an Ohio hospital setting, insurance coverages were based on the zip code 44106, and total expenses were based on all treatments plus a 5-year follow-up (not adjusted for inflation). Results: Treatment charges for ET include medical oncology initial consultation, biannual medical oncology follow-up, baseline bone density study, and Anastrozole cost (5-years). Treatment charges for RT include initial consultation, treatment planning, dosimetry calculations, treatment device, simulation and verification, RT delivery, on-treatment visits, and medical physics consultation. Original Medicare beneficiaries face an OOP cost of 20% for Medicare Part B claims with no cost cap for approved procedures after the deductible. Medications are covered under Medicare Part D with copays. This results in a marginal OOP treatment charge (after 5-year follow-up) of $767.54 for ET alone and $1,416.78 for ET + RT. Medigap Plan G beneficiaries face a marginal OOP charge of $1,225 for both ET alone and ET + RT, assuming the $226 Medicare Plan B deductible is met by the cost of lumpectomy during the year of RT. For Medicaid beneficiaries (assuming all treatments are approved by Medicaid), all expenses are covered without limit, resulting in no OOP expense for either treatment plan. Conclusions: Discussions of adding RT to ET for post-lumpectomy early-stage BC often involves considerations of treatment costs. This model (based on actual cost estimates per insurance plan rather than claims data) can help to enhance cost transparency by comparing expenses between Medicare and Medicaid plans.
Phase 1 dose-escalation, dose-expansion trial of intratumoral HER2- and HER3-primed dendritic cells injections for the treatment of early-stage TNBC and HR low positive breast cancer: DecipHER trial.
Authors: Ricardo L Costa, Jennifer A Childress, Edith Abraham, Carly Farrell, Qianxing Mo, Zena Jameel, Aixa Elena Soyano Muller, Kimberley T Lee, Susan Hoover, John Kiluk, Robert J Weinfurtner, Marie Catherine Lee, Christine Laronga, Nazanin Khakpour, Hyo S. Han, Hung T. Khong, Hatem Hussein Soliman, Brian J. Czerniecki
Journal: Journal of Clinical Oncology (2023)

TPS629 Background: Patients with breast cancers (BCs) harboring low expression of hormone receptors (HRs) and human epidermal growth factor receptor-2 (HER2) have poor outcomes. Results from the KEYNOTE-522 trial showed that activation of the immune system using a PD1/PD-L1-targeted approach improves outcomes of patients with these high-risk tumors. Antigen-presenting cells (eg, dendritic cells [DCs]) are pivotal for robust cytotoxic responses due to broader activation of the adaptive immune system (ie, CD4 + and CD8 + Th1) against tumor-associated antigens (ie, HER2 or HER3) expressed by high-risk BCs. Methods: DecipHER is a dose-escalation, dose-expansion phase 1 trial designed to assess the safety and the preliminary efficacy of autologous, HER2- and HER3-primed DCs in combination with KEYNOTE 522 regimen in 30 patients. Patients with clinical stage cT1cN1/2 or cT2-4cN0-2, HR 20, HER2-negative BCs are eligible. Patients with inflammatory BC cancer and uncontrolled immune mediated diseases are excluded. After collection through aphaeresis, autologous DCs will be primed ex vivo against 6 HER2 and 8 HER3 immunogenic peptides. Participants will receive alternating ultrasound-guided intratumoral HER2 and HER3 DC injections administered twice a week for 8 doses in total starting 2 weeks prior to neoadjuvant therapy with KEYNOTE 522 regimen. The dose-escalation phase of the study has 3 planned cohorts (10-20, 30-50, 80-100 million DCs) and follows a 3+3 design (maximum n=18). The 12 additional patients enrolled will be treated at the maximum tolerated dose (MTD) in the dose-expansion cohort. The MTD will be defined as the highest dose level at which &lt; 2 of 6 patients experience dose-limiting toxicities (grade ≥ 3 non-hematologic, ; grade ≥ 3 hematologic toxicity thought be at least possibly related to DCs ; any grade 4 nausea, vomiting, or diarrhea [or grade 3 if duration &gt; 3 days]) during the 5 weeks following treatment initiation with DCs. Secondary endpoints include the absolute risk of adverse events, clinical and pathological responses, and recurrence free survival. Tumor tissue, blood and stool samples will be collected for correlative analyses. The study is open at H. Lee Moffitt Cancer Center. Clinical trial information: NCT05504707 .
Treatment outcomes in patients with discordant recurrence score and RSClin risk predictions.
Authors: Augustin Vannier, Asim Dhungana, Fangyuan Zhao, Nan Chen, Sarah Shubeck, Olwen Mary Hahn, Rita Nanda, Nora T. Jaskowiak, Gini F. Fleming, Olufunmilayo I. Olopade, Alexander T. Pearson, Dezheng Huo, Frederick Matthew Howard
Journal: Journal of Clinical Oncology (2023)

574 Background: Guidelines recommend the use of genomic assays to aid decision making regarding the use of adjuvant chemotherapy (CT) for hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer (EBC). Recently, the RSClin tool, which integrates the 21-gene recurrence score (RS) and clinicopathologic features, was developed to better estimate CT benefit. Here, we studied patients with RSClin/RS discordance to determine if patients (pts) should be treated according to RS or RSClin. Methods: This was a retrospective cohort study of pts from the National Cancer Database who were diagnosed with HR+/HER2- node negative EBC from 2010-2020 who underwent RS testing and received adjuvant endocrine therapy with or without CT. Pts were classified as low RS ( &lt; 26) or high RS (≥ 26) and low ( &lt; 3%) versus high (≥ 3%) predicted CT benefit per RSClin. The primary outcome was overall survival (OS) benefit associated with CT administration for pts with discordant RS/RSClin, measured as hazard ratio [HR] for receipt of CT. Hazard ratios were adjusted for age and comorbidity index, and inverse probability of treatment weighting was performed for age, comorbidity index, race, ethnicity, and insurance status. Results: 262,748 pts with EBC were included, with a median follow-up of 58 months. Median age was 60 years; 82% were White, 7% Black, 5% Hispanic, and 4% Asian/Pacific Islander. Median tumor size was 1.5 cm, and median RS was 15. The 31,955 cases with concordant high RS/RSClin had an OS benefit with CT (HR: 0.71, 95% CI: 0.67 - 0.75, p &lt; 0.001), while the 206,631 cases with concordant low RS/RSClin did not have a survival benefit (HR: 1.00, 95% CI: 0.95 - 1.04, p = 0.85, Table). High RS with low RSClin was seen in 435 cases – all with grade 1 tumors, with RS no greater than 28, and tumor size under 1.3cm. No significant CT benefit was seen in this small subset of pts (HR 1.57, 95% CI 0.75 – 3.26, p = 0.23). In 23,727 pts with low RS but high RSClin, a CT benefit was seen (HR 0.73, 95% CI 0.67 – 0.78, p &lt; 0.001). These pts had high-intermediate RS (median 23, interquartile range 20 – 24) with other higher risk features. Similar results were seen in older (age &gt; 50) and younger (age ≤ 50) subgroups – although no pts ≤ 50 were in the low RS/high RSClin group. Conclusions: RSClin may identify a small number of grade 1 tumors with high RS for which CT is not needed, and may help guide appropriate use of CT for EBC in the sizeable group with intermediate RS. [Table: see text]
Association of <i>KMT2C </i>loss-of-function mutations in circulating tumor DNA and prolonged response to the combination of PARPi and PI3Ki.
Authors: Felipe Batalini, Shizong Ke, Ruolin Liu, Tim Blewett, Justin Rhoades, Doga Gulhan, Panagiotis A. Konstantinopoulos, Ursula A. Matulonis, Viktor Adalsteinsson, Gerburg M. Wulf
Journal: Journal of Clinical Oncology (2023)

e13003 Background: The emergence of somatic KMT2C mutations has been associated with resistance to various treatments, including chemotherapy and endocrine therapy in patients with estrogen receptor-positive breast cancers. The impact of these mutations in patients treated with poly-ADP ribose polymerase inhibitors (PARPi) and phosphatidylinositol-3-kinase inhibitors (PI3Ki) is unknown. Methods: Circulating tumor DNA (ctDNA) was obtained from plasma and peripheral blood at different time points from 38 patients prior to treatment with the combination of the PARPi olaparib with the alpha-specific PI3Ki alpelisib (NCT01623349). CtDNA was also collected immediately before the first cycle and at the time of disease progression. CtDNA underwent deep targeted sequencing (tumor-normal pairs, 397 genes (2Mb) at 25,000x somatic and 10,000x germline) at the Broad Institute of MIT and Harvard. Variants that were exonic, non-synonymous, and predicted to lead to loss-of-function were considered mutations. Cohorts were stratified according to the presence or absence of the genomic alteration, and progression-free survival was compared with the Kaplan-Meier method and log-rank test. A Cox regression was performed using age, tumor type, germline BRCA1/2 mutation status, performance status, and number of previous lines of treatment as covariates. Results: The KMT2C gene was one of the 3 genes most frequently mutated in our cohort, affecting 5 patients (15%) after the exclusion of those with variants with non-deleterious alterations. The other 2 commonly mutated genes were TP53 (76%) and PIK3CA (15%). In the comparison of patients based on these most common mutations, we identified that patients with somatic KMT2C mutations (n=5) have longer mPFS than those that were wild type (n=28): mPFS 386 vs. 151 days, log-rank p = 0.025. Cox proportional hazards model accounting for age, tumor type, germline BRCA1/2 mutation status, performance status, and number of previous lines revealed a hazard ratio of 0.16; p = 0.007. All somatic KMT2C mutations were proximal to the SET domain critical for methyltransferase activity. Upon progression, the KMT2C-mutated clones were suppressed to below the detection level of mutation calling algorithms. Analysis of the raw files revealed that the clones were suppressed but not eliminated. Conclusions: While the emergence of KMT2C has been reported to be associated with cancer progression and resistance to different therapies, patients with deleterious KMT2C mutations in the ctDNA may benefit from therapy with PARPi and PI3Ki.
Analyzing free-text clinical narratives for veterans with lymphoid malignancies using natural language processing (NLP).
Authors: Lu He, Matthew Moldenhauer, Kai Zheng, Helen Ma
Journal: Journal of Clinical Oncology (2023)

e13576 Background: Free-text clinical narratives contain rich patient information, which is labor-intensive to extract through chart review. We developed an NLP pipeline to enable automatic extraction of performance status (PS), staging, and diagnosis from clinical narratives from Veterans Affairs (VA) patients with lymphoid malignancies (LM). Methods: The rule-based NLP algorithm was developed and iteratively refined using a development corpus of 287 notes independently annotated by two clinicians. The F1-score for PS was 95.8 (precision 98.6, recall 93.2), 92.7 for staging (precision 94.0, recall 81.6), and 67 (precision 80.2, recall 57.9) for diagnosis. The NLP pipeline was then externally validated using an evaluation corpus of 97 notes from another group of 100 veterans with T-cell LM. Results: The results are reported. In the 97 notes, primary diagnosis was most routinely documented, with 2.76 mentions per note. In comparison, staging was most sparsely documented with only 34 mentions (note that 11 patients with large granular lymphocytic leukemia were not staged). The NLP pipeline performed relatively well in extracting PS and staging (F1-scores were 0.74 and 0.72, respectively). It also achieved high precision in extracting diagnosis information (precision 0.93). However, recall (0.44) for diagnosis was poor, likely due to the complexities and inconsistencies of how diagnoses are documented for LM. Frequency of documentation and performance in the external validation set. Conclusions: The pipeline shows promising performance on the external validation set, demonstrating the feasibility of using NLP to extract information from notes of patients with LM for clinical research. The NLP pipeline generally has lower recall than precision, indicating that the pipeline may miss clinical information that should be captured. FPs incorrectly capture entities that are easily confused with the clinical entities of interest, such as nutritional status versus performance status. Future work includes capturing more lexical variations and indicators of documentation, as well as contextual information, such as in which sections of notes elements are likely documented. In addition, we describe how diagnosis may exist as primary, secondary, and in a differential, and we are building an NLP-based classifier to distinguish between these types of diagnoses. We will use results from the rule-based NLP pipeline as labels to fine-tune transformer-based, weak-supervised models to further enhance the performance. [Table: see text]
Implementation of an early-stage lung cancer survivorship clinic in a comprehensive cancer center.
Authors: Stacy Wentworth, Alana Willis, Amy E. Hensley, Jill Hyson, Stephanie Jean Sohl, Ralph D'Agostino, Alberto de Hoyos, William J. Petty, A. William Blackstock
Journal: Journal of Clinical Oncology (2023)

e13515 Background: Early-stage lung cancer survivors are a growing population. A comprehensive plan to address needs relevant to longer survival (e.g., psychological distress, persistent symptoms, physical function) and clinic capacity is necessary. How to deliver comprehensive survivorship care that meets national standards and results in improved patient outcomes is a challenge. Survivorship clinics staffed by advanced practice providers (APP) are an option to address these needs. Methods: In June 2019, Atrium Health Wake Forest Baptist Comprehensive Cancer Center (AHWFB-CCC) opened a dedicated survivorship clinic. Stakeholders from the lung cancer disease-oriented team developed a standard referral pathway for patients to survivorship. A standard workflow was developed in the electronic medical record (EPIC). Eligible lung cancer survivors were referred to the Lung Cancer Survivorship Clinic for a survivorship orientation visit (SOV) with a lung cancer specific APP. Prior to the SOV, a welcome video, disease-specific questionnaire, and electronic patient reported outcome (ePRO) tools (i.e., PROMIS-29 and Distress Thermometer) were sent to the patients’ electronic chart. At the SOV, the ePRO responses and survivorship care plan were reviewed. Analysis of survivor demographic and clinical characteristics (i.e., age, gender, race, residence according to rural-urban commuting area (RUCA) codes, treatment modality, and method used to complete ePROs) and ePRO responses was performed using several regression methods. Patients were offered a post visit survey. Results: From January 2020 to December 2022, 285 lung cancer patients completed a SOV. Most patients were able to complete the pre-visit questions via the electronic chart. AHWFB-CCC survivors reported improved PROMIS-29 T-Scores compared to the average United States (US) early-stage lung cancer survivor, with meaningfully better scores (≥ 3 pts) in five of the seven health-related domains measured. We found no significant interactions between T-Scores and a survivor’s demographic or clinical characteristic, except for gender (p &lt; .001). Most notably, we found a lack of interaction between PROMIS-29 T-Scores and treatment modality (p=.27). Most patients found the SOV helpful and expressed better understanding of their cancer treatment and side effects after the SOV. Conclusions: Our model of an optimized electronic medical record pathway paired with an APP led survivorship visit is feasible and can address current challenges in providing survivorship care to early-stage lung cancer survivors. Survivors had similar ePRO regardless of treatment modality, indicating their survivorship care could be consolidated. Future evaluation is needed to establish if this care model improves outcomes over subsequent visits, minimizes the effect of health disparities, or enhances care capacity.
Mixed-methods clinical trial to evaluate the feasibility of the CURATE.AI optimised digital cognitive rehabilitation therapeutic (COR-Tx) in patients post brain radiotherapy.
Authors: Marlena N. Raczkowska, Alexandria Remus, Smrithi Vijayakumar, Siong Peng Kwek, V Vien Lee, Xavier Tadeo, Grady Ng, Ni Yin Lau, Qiao Ying Leong, Qian Yee Chai, Fatin Aliyah, Agata Blasiak, Wei Tsau David Chia, Christopher L. Asplund, Dean Ho, Balamurugan A. Vellayappan
Journal: Journal of Clinical Oncology (2023)

TPS1615 Background: Cognitive decline may be exacerbated, in brain tumour patients, by prior radiotherapy (RT). Traditional interventions to mitigate this typically involve fixed dose or intensity pharmacological and/or cognitive rehabilitation therapies that often elicit sub-optimal or no response, due to the dynamically evolving patient state and low adherence. Personalised digital therapeutics (DTx) may be more effective for this population. Further, gamification has previously shown to induce positive health behavioural change and improve intervention adherence. To this end, we have developed the CURATE.AI COR-Tx platform, a gamified DTx, that combines a previously validated, small-data artificial intelligence-derived dose optimisation technology with digital multitasking cognitive training. This novel DTx dynamically personalises treatment by using the patient’s own longitudinal performance data to generate an evolving digital avatar that guides training intensity throughout the intervention. Herein, we aim to evaluate feasibility, user experience and usability of the DTx platform in brain tumour patients post-RT. Methods: This is a prospective, mixed-methods, interventional, single-arm, decentralised feasibility clinical trial. The primary objective is to evaluate feasibility of the CURATE.AI COR-Tx platform as both a digital intervention (DI) and digital diagnostic (DD) for cognitive function in 15 patients with brain tumour post-RT. The personalised and home-based DI involves completing three 12-min sessions per week for 10 weeks, starting 1 month post-RT. Cognitive function will be assessed via a combined non-digital cognitive evaluation and a DD session at five time points: prior to RT, pre- &amp; post-DI and 16- and 32-weeks post-DI. Feasibility outcomes relating to acceptability, demand, implementation, practicality and limited efficacy testing and additional secondary and exploratory outcomes relating to usability and user experience will be collected by the clinical team and through semi-structured patient interviews and a study team focus group discussion at study completion. We will adopt a mixed-methods approach for data analysis. Feasibility of the CURATE.AI COR-Tx platform will be evaluated through thematic analysis for qualitative outcomes (acceptability and practicality), and descriptive and correlational analysis for quantitative outcomes (demand and implementation). We will adopt the CONSORT traffic light system to decide on future expansion into a large-scale randomised control trial. This trial began in April 2021 and has enrolled 14 of planned 15 patients at the time of submission. Clinical trial information: NCT04848935 .
Imbalance in treatment discontinuation without progression between experimental and control arms among randomized trials in advanced breast cancer.
Authors: Faris Tamimi, Abhenil Mittal, Consolacion Molto, Diego Malon Gimenez, Michelle B. Nadler, Eitan Amir
Journal: Journal of Clinical Oncology (2023)

1110 Background: In Randomized Controlled Trials (RCT), treatment discontinuation (TD) can result in censoring. Imbalanced frequency of TD between arms could impact interpretation of results. Here, we quantify TD between the experimental and control arms among RCT supporting registration of drugs for advanced breast cancer. Methods: We identified RCT supporting US Food and Drug Administration's approval of drugs for advanced breast cancer between 2013 and 2023. We extracted data for the number of participants with TD for reasons other than disease progression (PD), death, or completion of treatment. Odds ratio (OR) for TD comparing experimental to control arms were determined for each trial. To assess progression-free survival (PFS) translation into an overall survival (OS) benefit, we calculated hazard ratio (HR) for PFS/OS. Then we assessed whether there was quantitative association between the OR for TD and the ratio of HR for PFS/OS. Quantitative significance was defined according to the criteria of Burnand. Results: Analysis included 22 RCT comprising 13853 participants and supporting approval for 18 distinct drugs. TD was reported in 2212 (16.0%) participants. Among these participants, the leading causes of TD were withdrawal of consent (27.8%), site termination (20.7%), adverse events (17.2%), and loss of follow-up (10.9%). There was a statistically significant imbalance in the experimental arm in 4 RCT (18%) (Table), which was observed for everolimus, ribociclib (with fulvestrant), alpelisib, and neratinib. The OR for TD showed quantitative, but not statistically significant negative association with the ratio of the HR for PFS/OS (Beta -0.393; p=0.18). Conclusions: TD without PD, death, or completion of treatment occurs in a substantial proportion of participants of several RCT supporting approval of drugs for advanced breast cancer. all the statistically significant imbalanced TD in the RCT were in experimental arms. Quantitative association between imbalanced TD and the ratio of HR for PFS/OS suggests imbalanced TD may impact ability to translate improvements in PFS to OS. Results of RCT with imbalance in TD should be interpreted cautiously. [Table: see text]